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Clinical Features of Primary Immunodeficiency

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Clinical Features of Primary Immunodeficiency Clinical Features of Primary Immunodeficiency David Kiptum Introduction • Primary Immunodeficiency diseases are a group disorders caused by genetic defects of the immune system • Rare – 1:10,00 – 1:100,000 • Early detection is critically reducing morbidity and mortality • Children with severe, recurrent, or unusual infections may have a PID 2019 25, October Friday, Parts of the Immune System • B-Lymphocytes • T-Lymphocytes • Phagocytic System • Complement System • They each have specific roles, but work best in concert with the others Friday, October 25, 2019 25, October Friday, Rationale • Early diagnosis is important so that appropriate therapy can be instituted before organ damage • Early diagnosis is essential for making genetic information available to the families of affected individuals Friday, October 25, 2019 25, October Friday, Infectious Manifestations • Increased susceptibility – Chronic, recurrent infections • Infection with organism of low virulence (Aspergillus, Candida, Pneumocystis) • Infection of unusual severity (Sepsis, Empyema, Fistula) • Autoimmune or inflammatory disease • Syndrome Complex 2019 25, October Friday, Prediction • Cell Mediated Immunity deficiency- difficulty with viruses and fungi • Antibody deficiencies - encapsulated bacteria and enteroviruses Friday, October 25, 2019 25, October Friday, Prediction • Complement deficiencies - bacteremia, septic arthritis and meningitis, caused by encapsulated bacteria • Phagocytic disorders - infections of the skin and reticuloendothelial system (lymph nodes, spleen and liver) Friday, October 25, 2019 25, October Friday, Autoimmune and Inflammatory Manifestations • The basic abnormality leading to immunodeficiency may also lead to faulty discrimination between self and non-self, and thus to autoimmune disease • May be limited to a single target cell or organ or may involve several different target organs • Common in some PIDDs 2019 25, October Friday, Autoimmune and Inflammatory Manifestations • A disorder that appears to be autoimmune in nature may, in fact, be due to a viral agent • Target Cells – Hemolytic anemia – Immune thrombocytopenia – Thyroiditis Friday, October 25, 2019 25, October Friday, Autoimmune and Inflammatory Manifestations • Target Tissues – Vasculitis – Systemic lupus erythematosus – Rheumatoid arthritis • Associated Diseases – Common variable immunodeficiency – Selective IgA deficiency – Chronic mucocutaneous candidiasis 2019 25, October Friday, – Complement pathway deficiencies Immunodeficiency Diseases • Immunodeficiency can also be one part of a constellation of signs and symptoms in a syndrome complex • Recognition that a patient has a syndrome in which immunodeficiency occurs may allow a diagnosis of immunodeficiency to be made before there are any clinical manifestations of that deficiency 2019 25, October Friday, Immunodeficiency Diseases • DiGeorge syndrome – Congenital heart disease Hypoparathryroidism – Abnormal facies – Thymic hypoplasia • Wiskott-Aldrich syndrome – Eczema, Thrombocytopenia – Variable B- and T- lymphocyte dysfunction 2019 25, October Friday, Immunodeficiency Diseases • Ataxia-Telangiectasia – Ataxia-Telangiectasia – Variable B- and T- lymphocyte dysfunction • Ivemark syndrome – Bilateral 3-lobed lungs, Congenital heart disease – Asplenia Friday, October 25, 2019 25, October Friday, Immunodeficiency Diseases • Polyendocrinopathy syndrome – Endocrine organ dysfunction – Chronic mucocutaneous candidiasis Friday, October 25, 2019 25, October Friday, 10 Warning Signs of Immunodeficiency • ≥ 4 new ear infections within 1 year • ≥ 2 serious sinus infections within 1 year • ≥ 2 months on antibiotics with little effect • ≥ 2 pneumonias within 1 year • Failure of an infant to gain weight or grow normally Friday, October 25, 2019 25, October Friday, 10 Warning Signs of Immunodeficiency • Recurrent, deep skin or organ abscesses • Persistent thrush in mouth or fungal infection on skin • Need for IV antibiotics to clear infections • ≥ 2 deep-seated infections including septicemia • A family history of PID Friday, October 25, 2019 25, October Friday, Most Useful Warning Signs • Positive family history (RR = 18; 95% CI, 8 to 45 for any type of primary immunodeficiency disease); • A diagnosis of sepsis treated with intravenous antibiotics (RR = 5; 95% CI, 1.4 to 15 for phagocytic disorders) • Failure to Thrive Friday, October 25, 2019 25, October Friday, Initial Laboratory Work Up • HIV Screening • Haemogram • Immunoglobulin Levels • Complement Levels • Further Testing – Guided by Clinical Features Friday, October 25, 2019 25, October Friday, Specific Tests Screening Tests for Primary Immunodeficiency Suspected Abnormality Diagnostic Tests Antibody Quantitative immunoglobulins (IgG, IgA, IgM) Antibody response to immunization Cell Mediated Immunity Lymphocyte count T lymphocyte enumeration (CD4, CD8) HIV serology Delayed type hypersensitivity skin tests Complement Total hemolytic complement (CH50) Phagocytosis Neutrophil count Nitroblue tetrazolium (NBT) dye test 2019 25, October Friday, Resources • European Society for Immunodeficiencies http://www.esid.org • Immune Deficiency Foundation/The National Patient Organization for Primary Immunodeficiency Diseases http://www.primaryimmune.org • U.S. Immunodeficiency Network http://www.usidnet.org 2019 25, October Friday, Management • Manage Infections – Prevent, Treat – Treat Symptoms • Boost Immune System – Immunoglobulin Therapy – Interferon Gamma Therapy – Growth Factors • Stem Cell Transplant 2019 25, October Friday,.
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